{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T17:39:41Z","timestamp":1787938781826,"version":"build-2784847793"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":1244,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["5T32HL007749-27"],"award-info":[{"award-number":["5T32HL007749-27"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01BX000656"],"award-info":[{"award-number":["I01BX000656"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK6BX003615-01"],"award-info":[{"award-number":["IK6BX003615-01"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["CX001553"],"award-info":[{"award-number":["CX001553"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Disseminated cryptococcosis has a nearly 70% mortality, mostly attributed to CNS infection, with lesser-known effects on other organs. Immune protection against Cryptococcus relies on Th1 immunity with M1 polarization, rendering macrophages fungicidal. The importance of M1-upregulated inducible NO synthase (iNOS) has been documented in pulmonary anticryptococcal defenses, whereas its role in disseminated cryptococcosis remains controversial. Here we examined the effect of iNOS deletion in disseminated (i.v.) C. deneoformans 52D infection, comparing wild-type (C57BL\/6J) and iNOS\u2212\/\u2212 mice. iNOS\u2212\/\u2212 mice had significantly reduced survival and nearly 100-fold increase of the kidney fungal burden, without increases in the lungs, spleen, or brain. Histology revealed extensive lesions and almost complete destruction of the kidney cortical area with a loss of kidney function. The lack of fungal control was not due to a failure to recruit immune cells because iNOS\u2212\/\u2212 mice had increased kidney leukocytes. iNOS\u2212\/\u2212 mice also showed no defect in T cell polarization. We conclude that iNOS is critically required for local anticryptococcal defenses in the kidneys, whereas it appears to be dispensable in other organs during disseminated infection. This study exemplifies a unique phenotype of local immune defenses in the kidneys and the organ-specific importance of a single fungicidal pathway.<\/jats:p>","DOI":"10.4049\/jimmunol.2100386","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T18:25:25Z","timestamp":1630693525000},"page":"2096-2106","source":"Crossref","is-referenced-by-count":14,"title":["Murine Inducible Nitric Oxide Synthase Expression Is Essential for Antifungal Defenses in Kidneys during Disseminated <i>Cryptococcus deneoformans<\/i> Infection"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2915-6765","authenticated-orcid":false,"given":"Kristie D","family":"Goughenour","sequence":"first","affiliation":[{"name":"Research Service, VA Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1323-2030","authenticated-orcid":false,"given":"Jessica","family":"Zhao","sequence":"additional","affiliation":[{"name":"Research Service, VA Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintao","family":"Xu","sequence":"additional","affiliation":[{"name":"Research Service, VA Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5457-059X","authenticated-orcid":false,"given":"Ziyin P","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anutosh","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI"},{"name":"Department of Surgery, University of Michigan , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M","family":"Freeman","sequence":"additional","affiliation":[{"name":"Research Service, VA Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7474-0843","authenticated-orcid":false,"given":"Michal A","family":"Olszewski","sequence":"additional","affiliation":[{"name":"Research Service, VA Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"2025030418555616200_r1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/QAD.0b013e328322ffac","article-title":"Estimation of the current global burden of cryptococcal meningitis among persons living with HIV\/AIDS","volume":"23","author":"Park","year":"2009","journal-title":"AIDS"},{"key":"2025030418555616200_r2","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S1473-3099(17)30243-8","article-title":"Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis","volume":"17","author":"Rajasingham","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"2025030418555616200_r3","first-page":"61","article-title":"Cryptococcal infections in non-HIV-infected patients","volume":"124","author":"Pappas","year":"2013","journal-title":"Trans. Am. Clin. Climatol. Assoc."},{"key":"2025030418555616200_r4","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1086\/507895","article-title":"Symptomatic relapse of HIV-associated cryptococcal meningitis after initial fluconazole monotherapy: the role of fluconazole resistance and immune reconstitution","volume":"43","author":"Bicanic","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"2025030418555616200_r5","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1086\/313757","article-title":"Practice guidelines for the management of cryptococcal disease","volume":"30","author":"Saag","year":"2000","journal-title":"Clin. Infect. 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